Disitamab vedotin (RC48) is an antibody-drug conjugate (ADC) comprising a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) conjugated via a cleavable linker to the cytotoxic agent Monomethyl auristatin E (MMAE). Disitamab vedotin enhances antitumor immunity[1].
IC50 & Target[1]
HER2
体外研究 (In Vitro)
The antibody part was a humanized monoclonal antibody targeting HER2, the small molecule toxin was monomethyl auristatin E (MMAE), a synthetic antineoplastic agent. A protease cleavable linker covalently attached MMAE to the antibody[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
CAS 号
2136633-23-1
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Deeks ED. Disitamab Vedotin: First Approval. Drugs. 2021;81(16):1929-1935.
[2]. Jiang J, et al. Preclinical safety profile of disitamab vedotin：a novel anti-HER2 antibody conjugated with MMAE. Toxicol Lett. 2020;324:30-37.
H-DPhe-Cys-Tyr-DTrp-Lys-Val-Cys-Trp-NH2?(trifluoroacetate salt)(Cys2 and 7 bridge)
基本描述
Peptide that arises from the posttranslational cleavage of prosomatostatin, which in turn is derived from a large precursor, preprosomatostatin. It was found in the central and peripheral nervous system, the gastrointestinal (GI) tract. It additionally increases amylase secretion, cellular cycle GMP, and Ca 2+ outfluxes.
溶解度
分子量
1133.4
化学式
C57H72N12O9S2
存储条件
Store at -20°C. Keep tightly closed. Store in a cool dry place.
Vapreotide acetate (RC-160 acetate; BMY-41606 acetate) is a neurokinin-1 (NK1) receptor antagonist, with an IC50 of 330 nM.
体外研究 (In Vitro)
Vapreotide attenuates the Substance P (SP)-triggered intracellular calcium increases and NF-κB activation in a dose-dependent manner. Vapreotide also inhibits SP-induced IL-8 and MCP-1 production in HEK293-NK1R and U373MG cell lines. Vapreotide inhibits HIV-1 infection of human MDM in vitro, an effect that is reversible by SP pretreatment[1]. Vapreotide significantly inhibits GH-, PRL, and/or alpha-subunit release by human GH-secreting pituitary adenoma cells in concentrations as low as 10-12-10-14 M. Vapreotide inhibits GH release with an IC50 of 0.1 pM[2]. Vapreotide exhibits moderate-to-high affinities for SSTR2, -3, and -5 (IC50=0.17, 0.1 and 21 nM, respectively) and low affinity for SSTR1 and -4 (IC50=200 and 620 nM, respectively). RC-160 inhibits serum-induced proliferation of CHO cells expressing SSTR2 and SSTR5 (EC50=53 and 150 pM, respectively)[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
In cirrhosis, bleeding by rupture of oesophagogastric varices is a severe complication of portal hypertension. The acute administration of vapreotide to rats decreases collateral circulation blood flow while chronic administration attenuated its development[4]. Tumor volumes and weights are reduced by about 40% by RC-160 by s.c. injections at doses of 100 μg/day/animal. Vapreotide can inhibit the growth of androgen-independent prostate cancer when the therapy is started at an early stage of tumor development[5].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
1191.39
Formula
C57H70N12O9S2.xC2H4O2
CAS 号
849479-74-9
中文名称
醋酸伐普肽
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Spitsin S, et al. Analog of somatostatin vapreotide exhibits biological effects in vitro via interaction with neurokinin-1 receptor. Neuroimmunomodulation. 2013;20(5):247-55.
[2]. Hofland LJ, et al. Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on theinhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells. Endocrinology. 1994 Jan;134(1):301-6.
[3]. Buscail L, et al. Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1580-4.
[4]. Veal N, et al. Hemodynamic effects of acute and chronic administration of vapreotide in rats with cirrhosis. Dig Dis Sci. 2003 Jan;48(1):154-61.
[5]. Pinski J, et al. Effect of somatostatin analog RC-160 and bombesin/gastrin releasing peptide antagonist RC-3095 on growth of PC-3 human prostate-cancer xenografts in nude mice.
Cell Assay [3]
CHO cells are cultured in aMEM containing 10% FCS. After overnight attachment, the medium is changed to a MEM containing either 10% FCS or insulin with and without vapreotide. Cell growth is measured after 24 h by counting cells with a Coulter counter model ZM[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [4][5]
Rats: Acute effects are evaluated at baseline and 30 min after placebo or vapreotide (8 μg/kg/hr) infusions in DMNA rats. Chronic hemodynamic effects are evaluated using subcutaneous implants for five weeks in anesthetized DMNA rats and in sham rats. Hemodynamic measurements include splenorenal shunt blood flow by the transit time ultrasound method and cardiac output by the combined dilution–TTU method[4].
Mice: Nude mice bearing xenografts of the androgen-independent human prostate-cancer cell line PC-3 are treated for 4 weeks with somatostatin analog vapreotide (20 μg/day/animal), bombesin/gastrin-releasing peptide (GRP) antagonist, or the combination of both peptides. Tumor volumes and weights are measured[5].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Spitsin S, et al. Analog of somatostatin vapreotide exhibits biological effects in vitro via interaction with neurokinin-1 receptor. Neuroimmunomodulation. 2013;20(5):247-55.
[2]. Hofland LJ, et al. Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on theinhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells. Endocrinology. 1994 Jan;134(1):301-6.
[3]. Buscail L, et al. Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1580-4.
[4]. Veal N, et al. Hemodynamic effects of acute and chronic administration of vapreotide in rats with cirrhosis. Dig Dis Sci. 2003 Jan;48(1):154-61.
[5]. Pinski J, et al. Effect of somatostatin analog RC-160 and bombesin/gastrin releasing peptide antagonist RC-3095 on growth of PC-3 human prostate-cancer xenografts in nude mice.
In the FLIPR assay, Anamorelin (ANAM) shows significant agonist activity on the ghrelin receptor, with EC50 value of 0.74 nM. No significant antagonist activity is observed with Anamorelin at concentrations of up to 1,000 nM. In the binding experiments, Anamorelin binds to the ghrelin receptor with a binding affinity constant (Ki) of 0.70 nM. In the competition assay with radiolabeled ibutamoren (35S-MK-677; another ghrelin receptor agonist) Anamorelin (ANAM) is also found to bind with high affinity to the ghrelin receptor (IC50=0.69 nM). In rat pituitary cells incubated with Anamorelin, there is a dose-dependent stimulatory effect on GH release and the potency (EC50) is 1.5 nM. Anamorelin is screened for activity against a set of over 100 receptors, ion channels, transporters, and enzymes. Anamorelin demonstrates binding to the tachykinin neurokinin 2 (NK2) site (IC50=0.021 μM); however, a subsequent NK2 functional assay demonstrates no functional activity[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
In rats, Anamorelin (ANAM) at an oral dose of 3, 10, or 30 mg/kg once daily significantly increases both food intake and body weight from Day 2 to Day 7 of treatment compared with the vehicle control. The cumulative change in food intake and weight gain increases dose-dependently, and these changes are significant at all dose levels (P<0.05) compared to the control. Administration of Anamorelin at a single oral dose of 3, 10, or 30 mg/kg induces a dose-dependent increase in plasma GH levels and GH AUC0-6h in rats[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
583.16
Formula
C31H43ClN6O3
CAS 号
861998-00-7
中文名称
盐酸阿拉莫林
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Pietra C, et al. Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexiasyndrome: preclinical profile. J Cachexia Sarcopenia Muscle. 2014 Dec;5(4):329-37.
Kinase Assay [1]
For the competition assay, Anamorelin (ANAM) concentrations (1 pM-10 μM) are added to the membranes together with 35S-MK-677. Nonspecific binding is determined by adding 10 μM nonlabeled MK-677. The mixture is incubated at 30°C for 60 min, followed by application of the samples to GF/B filters, which has been pretreated with 0.5 % PEI for 60 min. The filters are subsequently washed in 0.9 % NaCl and counted using an OptiPhase counter[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Rats[1] For the assessment of food intake and body weight, rats are divided into four groups: Anamorelin 3 mg/kg (n=7), 10 mg/kg (n=7), or 30 mg/kg (n=7), or vehicle control (n=8), and 100 μL blood samples are collected before and 0.25, 0.5, 1, 2, 3, 4, 5, and 6 h after single dosing. Rats are anesthetized with sodium pentobarbital 64.8 mg/kg. A catheter filled with heparinized saline solution is inserted in the left femoral artery for blood collection and fitted with an extension tube, 1 mL sampling syringe, and a three-way cock to allow excess blood to return. Plasma levels of GH are measured immunochemically using a Rat Growth Hormone EIA kit and microplate reader. Measurements are performed in duplicate. Area under the GH concentration curve from 0 to 6 h (AUC0-6h) postdose and the time course of GH plasma concentrations are evaluated. Pig[1] In pigs (n=6 per group), Anamorelin is dosed directly into the gastric lumen via the dosing catheter. Blood samples are collected for the stimulation profile of GH at 30 and 15 min before, and 0, 5, 15, 30, 45, 60, and 120 min following dosing. Animals received either a single dose (3.5 mg/kg), or once-daily administration (1 mg/kg) for 7 days and stimulation profiles are taken after the first and seventh dose of Anamorelin. To assess IGF-1 levels, pigs receive either placebo or Anamorelin for 7 days (1 mg/kg/day), and the following 7 days the two treatments are crossed over. A single blood sample is taken once a day immediately before dosing.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Pietra C, et al. Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexiasyndrome: preclinical profile. J Cachexia Sarcopenia Muscle. 2014 Dec;5(4):329-37.
FKBP12 PROTAC RC32 (RC32) is a potent FKBP12 degrader based on PROTAC technology. FKBP12 PROTAC RC32 contains conjugation of Rapamycin (HY-10219) and a ligand for an Cereblon E3 ubiquitin ligase (Pomalidomide; HY-10984)[1].
IC50 & Target[1]
Cereblon
体外研究 (In Vitro)
FKBP12 PROTAC RC32 (RC32; 0.1-1000 nM; for 12 hours) results in 50% protein degradation (DC50) of ~0.3 nM after only 12 hours of treatment[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
Jurkat cells
Concentration:
0.1, 1, 10, 100, 1000 nM
Incubation Time:
For 12 hours
Result:
Resulted in 50% protein degradation (DC50) of ~0.3 nM after only 12 h of treatment.
体内研究 (In Vivo)
RC32 (RC32; i.p.; 30 mg/kg; twice a day; 1 day) degrades the FKBP12 protein in most of the organs of treated mice, except for the brain after only 1 day of treatment in mice[1]. RC32 (orally; 60 mg/kg; twice a day; for 1 day) significantly degrades FKBP12 in mice[1]. RC32 (i.p.; 8 mg/kg; twice a day; for 2 days) efficiently degrades the FKBP12 protein in most of the organs examined in Bama pigs (20 kg) [1]. RC32 (i.p.; 8 mg/kg; twice a day; for 3 days) efficiently degrades FKBP12 in the heart, liver, kidney, spleen, lung, and stomach of rhesus monkeys[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male and female mice[1]
Dosage:
30 mg/kg
Administration:
IP; twice a day; 1 day
Result:
Degraded the FKBP12 protein in most of the organs of treated mice after only 1 day of treatment.
分子量
1426.69
Formula
C75H107N7O20
CAS 号
2375555-66-9
运输条件
Room temperature in continental US; may vary elsewhere.
Vapreotide is a neurokinin-1 (NK1) receptor antagonist, with an IC50 of 330 nM.
IC50 & Target
330 nM (NK1R)[1].
体外研究 (In Vitro)
Vapreotide attenuates the effect of SP on calcium release in a concentration-dependent manner. The concentration required for Vapreotide to completely inhibit the effect of SP is about 100 times higher than that required for the NK1R antagonist aprepitant. The effect of Vapreotide on cell proliferation is mediated primarily by SSTR2. In order to further establish the NK1R antagonist effect of Vapreotide, U373MG cells are pretreated with SSTR2 selective antagonist CYN followed by incubation with Vapreotide and SP stimulation. The results show that pretreatment with CYN does not reverse the inhibitory effect of Vapreotide on SP-stimulated IL-8 mRNA expression. Vapreotide reduces HIV-1 replication in MDM as indicated by limited HIV gag mRNA expression compared to control MDM. In addition, SP treatment (10 μM) reverses Vapreotide inhibition of HIV-1 replication in MDM. This observation indicates that the inhibition of HIV-1 replication by Vapreotide is most likely due to its interaction with NK1R[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
[1]. Spitsin S et al. Analog of somatostatin vapreotide exhibits biological effects in vitro via interaction with neurokinin-1 receptor. Neuroimmunomodulation. 2013;20(5):247-55.
Cell Assay [1]
The HEK293-NK1R cells and U373MG cells are incubated with or without Vapreotide (0, 5, 10, 20 μM) for 10 minutes and then incubated with or without SP for 3 hours. In some experiments, cells are first incubated with CYN for 10 minutes, and then Vapreotide is added and incubated for an additional 10 minutes, followed by stimulation with SP for 3 hours. Mock treated cells are used as controls[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Spitsin S et al. Analog of somatostatin vapreotide exhibits biological effects in vitro via interaction with neurokinin-1 receptor. Neuroimmunomodulation. 2013;20(5):247-55.
Ginsenoside Rc, one of major Ginsenosides from Panax ginseng, enhances GABA receptorA (GABAA)-mediated ion channel currents (IGABA). Ginsenoside Rc inhibits the expression of TNF-α and IL-1β.
IC50 & Target[2]
TNF-α
IL-1β
体外研究 (In Vitro)
Ginsenoside Rc, one of major Ginsenosides from Panax ginseng, enhances γ-aminobutyric acid (GABA) receptorA (GABAA)-mediated ion channel currents. Ginsenoside Rc enhances GABA-mediated ion currents in oocytes expressing the GABAA receptor[1]. Ginsenoside Rc significantly inhibits the expression of macrophage-derived cytokines, such as TNF-α and IL-1β. Ginsenoside Rc also markedly suppresses the activation of TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. Ginsenoside Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling. Ginsenoside Rc suppresses the nuclear translocation of phospho-ATF-2 and phospho-FRA-1, whereas the translocation of p65 at its peak time points (30 and 60 min) is not decreased by Ginsenoside Rc treatment. Ginsenoside Rc regulates the expression of the proinflammatory cytokine TNF-α, which is produced by macrophages, by suppressing AP-1 activation[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
1079.27
Formula
C53H90O22
CAS 号
11021-14-0
中文名称
人参皂苷 Rc
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Lee BH, et al. Effects of Ginsenoside Metabolites on GABAA Receptor-Mediated Ion Currents. J Ginseng Res. 2012 Jan;36(1):55-60.
[2]. Yu T, et al. Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-bindingkinase 1/interferon regulatory factor-3 and p38/ATF-2. J Ginseng Res. 2017 Apr;41(2):127-133.
Kinase Assay [2]
To evaluate the effects of Ginsenoside Rc on kinase activity, immunoprecipitated TBK1, IKKε, and p38 are incubated in reaction buffer in the presence or absence of Ginsenoside Rc. The reactions are initiated by the addition of Mg-ATP. After a 30 min incubation at 30°C, the reactions are stopped by the addition of sample buffer and the samples are boiled. Kinase activity is assessed by immunoblotting with antibodies against the phospho-forms of IKKε, IRF-3, and ATF-2[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Lee BH, et al. Effects of Ginsenoside Metabolites on GABAA Receptor-Mediated Ion Currents. J Ginseng Res. 2012 Jan;36(1):55-60.
[2]. Yu T, et al. Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-bindingkinase 1/interferon regulatory factor-3 and p38/ATF-2. J Ginseng Res. 2017 Apr;41(2):127-133.
![RC-160 (Vapreotide) 编码 [103222-11-3]](http://www.fluoroprobe.com/wp-content/uploads/2022/10/20221006_633ed95d52cbd.png)
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